Camptothecin is an antitumor alkaloid contained in plants such as Camptotheca acuminata of Chinese origin, and has an extremely poor solubility in water, therefore, clinically usable water-soluble derivatives thereof have been studied. Further, it is known that introduction of a substituent such as a hydroxyl group, alkoxyl group, amino group and the like onto the benzene ring reinforces its effect (Non-patent Literature 1).
For example, Patent Literature 1 and Patent Literature 2 refer to a high-molecular weight derivative of camptothecin carrying bonded polyethylene glycol as a prodrug. These patents report optimization of the molecular weight of the polyethylene glycol portion, and simultaneously, also the importance of a spacer bonding the polyethylene glycol portion to camptothecin. It is desirable that the spacer is stably present during residence of the above-mentioned derivative in an organism and is cut quickly only at a target region. These literatures judge that a mere ester type bonded compound of alcohol shows slow hydrolysis rate at a target region and sufficient drug concentration cannot be obtained, and disclose spacers which are easily hydrolyzed at a target region.
As a water-soluble derivative of camptothecin, CPT-11 (7-ethyl-10-piperidinopiperidinocarbonyloxycamptothecin) is known (Non-patent Literature 1).
Further, Patent Literature 3 describes a high-molecular weight derivative of camptothecins which carries bonded polyglutamic acid.
On the other hand, Patent Literature 4 and Non-patent Literature 2 show that an aggregate of molecules obtained by bonding a drug to a block copolymer of polyethylene glycol and polyaspartic acid can form micelle thereby enhancing its water-solubility and increase the drug content per polymer molecule, Patent Literature 5 shows a polymer anticancer agent obtained by bonding an anticancer substance to a side chain carboxylic acid of a block copolymer of polyethylene glycol and polyglutamic acid, and Patent Literature 6 shows a polymer drug carrier obtained by bonding a hydrophobic substance to a side chain carboxylic acid of a block copolymer of polyethylene glycol and acidic amino acid polymer. However, Patent Literature 4, Patent Literature 5 and Patent Literature 6 do not describe a bonded compound of camptothecins.